POS1557 MUSCULOSKELETAL ULTRASOUND IN PATIENTS WITH HEREDITARY ANGIOEDEMA DUE TO C1-INHIBITOR DEFICIENCY: PROBING DISEASE ACTIVITY AND DAMAGE
Authors: P. Triggianese, G. Raffone, A. D’antonio, E. Greco, S. Modica, A. Bergamini, M. S. Chimenti
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Hereditary angioedema (HAE) due to C1 esterase inhibitor protein (C1INH) deficiency is a rare disorder (1:50000) that is characterized by widely variable and potentially fatal attacks of subcutaneous and submucosal swelling which are generally self-limiting. The defect of C1INH allows for a dysregulated kallikrein–kinin pathway, and thus for the overproduction of bradykinin with, in turn, the consequent activation of the bradykinin B2 receptors. The resulting increased vascular permeability induces painful angioedema attacks most often involving the hands. Musculoskeletal ultrasound (MSUS) enables evaluation of the soft tissues, providing additional and more accurate assessment of inflammation and visualization of structural damage. <h3>Objectives</h3> To explore the potential damage at the site of angioedema attack, we performed an US-study of hands and wrists in consecutive C1INH-HAE patients referring to the HAE Reference Centre at "Tor Vergata" University Hospital in Rome (Italy). <h3>Methods</h3> Consecutive C1INH-HAE patients underwent biochemical analyses and, in the same day, MSUS evaluation that has been performed by an expert rheumatologist at wrists and hands. The US (Esaote MyLab™X75, 4-15 MHz) semi-quantitatively graded subcutaneous tissue edema, synovitis/tenosynovitis-like lesions, erosions, osteophytes, and bone edema according to the 2021 Outcome Measures in Rheumatology (OMERACT). HAE Quality of Life Questionnaire (HAE-QoL) and HAE Activity Score (HAE-AS) were registered. <h3>Results</h3> 94 C1INH-HAE patients from 50 independent families (aged 43.2 ± 17 yrs) has been included, with 60% females and 20.6% smokers. All patients experienced recurrent acute attacks at the hands: a third of the cohort (31.3%) was on long-term-prophylaxis at the time of the study and 20% of subjects had the last acute attack more than 12 months before. In 75% of the cohort, the HAE-QoL described a mild-moderate QoL and HAE-AS showed a mild disease activity. Smokers were prevalent among patients in high disease activity than in patients in low disease activity (P&lt;0.05). High level of C-reactive protein (≥5 mg/dl) has been documented in 13.8% of patients while rheumatoid factor and anti-cyclic-citrullinated-peptide-antibody (ACPA) resulted in rare cases (2.1% for both). A vitamin D deficiency (&lt; 7 ng/dl) has been registered in 3.6% of patients although insufficient vitamin D (7-30 ng/dl) resulted in 50% and hyperuricemia (&gt;7 mg/dl) in 4% of cases. ANA titer≥1:160 occurred in 25.5%. The joint pain at the hands/wrists have been reported by 70% of patients: patients with joint pain showed a lower mean C1INH antigen level and a higher number of attacks in the last 3 months than patients without (P&lt;0.05). Patients with at least 1 US lesion (62.8%) were significantly older and affected by a greater number of angioedema attacks than patients without lesions (37.2%, P&lt;0.05 for both). US lesions were mainly represented by osteophytes (63.5%) and cartilage damage (35.3%). Synovitis/tenosynovitis involving at least 1 joint has been documented in 44.7% of the cohort but a positive Power Doppler signal was revealed in rare cases (2.1%). The subcutaneous tissue edema resulted in a third of the cohort (29.8%). Cartilage damage and subcutaneous edema was similarly distributed among hands and wrists. The distal radioulnar joints were the most affected (25.5%) while metacarpophalangeal were affected in 17.6% of cases. Synovitis/tenosynovitis was mild-moderate in 98% of cases. In patients showing subcutaneous tissue edema, it was documented in 78.7% of cases at the hands and in 21.3% at the wrists. <h3>Conclusion</h3> C1-INH-HAE patients reported pain at joint level in an elevated frequency. Our findings support the role of MSUS in C1-INH-HAE patients by highlighting that US lesions at the specific sites of attacks, although mild, occur in more than a half of patients and appear to be linked with the age and/or disease duration and the number of attacks. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.